Chronic pain is one of the most prevalent health problems. The establishment of chronic pain is complex. Current medication for chronic pain mainly dependent on anticonvulsants, tricyclic antidepressants and opioidergic drugs. However, they have limited therapeutic efficacy, and some even with severe side effects. We turned our interest into alkaloids separated from traditional Chinese medicine (TCM), that usually act on multiple drug targets. In this article, we introduced the best-studied analgesic alkaloids derived from TCM, including tetrahydropalmatine, aloperine, oxysophocarpine, matrine, sinomenine, ligustrazine, evodiamine, brucine, tetrandrine, Stopholidine, and lappaconitine, focusing on their mechanisms and potential clinical applications. To better describe the mechanism of these alkaloids, we adopted the concept of drug-cloud (dCloud) theory. dCloud illustrated the full therapeutic spectrum of multitarget analgesics with two dimensions, which are “direct efficacy”, including inhibition of ion channels, activating γ-Aminobutyric Acid/opioid receptors, to suppress pain signal directly; and “background efficacy”, including reducing neuronal inflammation/oxidative stress, inhibition of glial cell activation, restoring the balance between excitatory and inhibitory neurotransmission, to cure the root causes of chronic pain. Empirical evidence showed drug combination is beneficial to 30–50% chronic pain patients. To promote the discovery of effective analgesic combinations, we introduced an ancient Chinese therapeutic regimen that combines herbal drugs with “Jun”, “Chen”, “Zuo”, and “Shi” properties. In dCloud, “Jun” drug acts directly on the major symptom of the disease; “Chen” drug generates major background effects; “Zuo” drug has salutary and supportive functions; and “Shi” drug facilitates drug delivery to the targeted tissue. Subsequently, using this concept, we interpreted the therapeutic effect of established analgesic compositions containing TCM derived analgesic alkaloids, which may contribute to the establishment of an alternative drug discovery model.

BackgroundImplant placement in the posterior maxilla is often complicated by the insufficient bone volume. While transalveolar sinus floor elevation (TSFE) has been proven as a predictable surgical procedure to increase the bone height in the posterior maxilla, questions in regard to the necessity of the bone grafting during the sinus lift and the question of whether TSFE could be performed when the residual bone height is below 5 mm are still debated. Furthermore, high-quality evidence comparing the clinical outcome of transalveolar sinus floor elevation with osteotome and modified sinus floor elevation with crestal non-cutting drills is limited.Methods/designOne hundred twenty adult patients who fit the inclusion criteria are being recruited from the Peking University Hospital of Stomatology First Clinical Division (Beijing, China). All patients are assigned to one of four groups according to a table of random numbers. Participants will receive (1) TSFE using osteotomes with bone grafting, (2) TSFE using osteotomes without bone grafting, (3) modified TSFE with bone grafting, or (4) modified TSFE without bone grafting. In a one-year follow-up period, implant survival rates, complications, implant stability, bone remodeling around the implant, and patient-reported outcome (visual analog scale for intraoperative discomfort and postoperative pain) will be observed and documented. The implant stability will be gauged by the resonance frequency analysis six times (at baseline and weeks 6, 8, 12, 16, and 26), and the bone remodeling will be observed and compared via radiographic examinations.DiscussionThe result of the trial will potentially contribute to better decision making in atrophic posterior maxilla when implant placement is needed. Therefore, if the outcome is deemed favorable, the use of the modified TSFE would achieve an outcome equivalent to that of the traditional TSFE while introducing less trauma and postoperative discomforts. Separately, whether the bone graft procedure is necessary for the TSFE will also be discussed.Trial registrationThe study has been registered in ClinicalTrials.gov under the identifier number NCT03445039. Registered on 26 February 2018.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2879-x) contains supplementary material, which is available to authorized users.

This systematic review and meta‐analysis aimed to evaluate the efficacy of vigabatrin (VGB) in treating infantile epileptic spasms syndrome (IESS). Databases of PubMed, Embase, Web of Science, MEDLINE, and Cochrane Library were systematically searched. All the relevant randomized controlled trials (RCTs) and observational studies (OSs) of VGB for IESS were included and analyzed separately. The primary outcome was the cessation of epileptic spasms (ES). Five RCTs and nine OSs compared the efficacy of VGB vs hormonal monotherapy for IESS. Meta‐analysis of the five RCTs showed that hormonal monotherapy was significantly better than VGB monotherapy (OR = 0.37, 95% CI = 0.20‐0.67) for patients with new‐onset IESS. Meta‐analysis of the nine OSs agrees with the result from RCTs (OR = 0.61, 95% CI = 0.43‐0.85). VGB was more effective in patients with TSC than in those with other etiologies (five OSs, OR = 5.59, 95% CI = 2.17‐14.41). There was no significant difference in the efficiency of VGB combined with hormonal therapy vs hormonal monotherapy for IESS (two RCTs, OR = 0.75, 95% CI = 0.09‐6.45). Hormonal monotherapy is better than VGB monotherapy for non‐TSC‐associated IESS. But for patients with IESS due to TSC, VGB is the first choice. VGB combined with hormone therapy does not definitely increase ES control rates compared with that of hormonal monotherapy.

ObjectiveTo analyze the clinical features, treatment, and prognosis of patients with vitamin B6-responsive infantile spasms (IS).MethodsThe clinical features, genetics, and follow-up data of 30 patients were collected and analyzed.ResultsThe age of epileptic spasms (ES) onset was from 3 months to 12 months. They all received high doses of vitamin B6 at different times after the onset of ES, ranging from 1 day to 5 months. ES were controlled within 11 days in 93% (28/30) patients, and as late as 1 month and 2 months in the other two patients. In the course of treatment, 28 patients were seizure-free all the time, and seizures of other two patients recurred due to withdrawal of vitamin B6. The available follow-up EEG results of 28 patients were normal in 26 cases, and 81% (21/26) had suppressed epileptic discharges within 6 months. Of the 26 cases with normal follow up EEG, 4 had developmental delay and 22 had normal development. The time for EEG to return to normal in 22 patients with normal development ranged from 14 days to 2 years (mean = 111.5 days; median = 52.5 days). The time for EEG to return to normal in the other 4 patients with development delay ranged from 4 months to 2 years (mean = 375 days; median = 330 days). To the last follow-up, seizures were controlled well in 29 surviving patients, and 21 patients were able to deactivate from all medications without seizures recurrence. Sixteen patients showed varying degrees of developmental delay after onset. After seizure control, the psychomotor development was delayed in 7 patients (one died) until the last follow-up. Genetic analysis did not show any meaningful results.ConclusionAn observation period of 1–2 weeks is essential to identify patients with vitamin B6-responsive IS. The treatment time could be extended according to the treatment response and EEG changes. It might take a longer time for EEG to return to normal and to stop taking drugs in patients with persistent or unimproved developmental delay. Neurodevelopmental outcomes and prognosis of vitamin B6-responsive IS were relatively favorable.

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